1. Field of the Invention
The present invention relates to a medical image processing apparatus that makes a determination regarding the presence of a tumor based on ultrasonic images acquired by capturing a subject to which a contrast agent has been administered. The present invention also relates to an ultrasonic imaging apparatus that makes a determination regarding the presence of a tumor based on ultrasonic images.
2. Description of the Related Art
“Malignant neoplasm (cancer)”, “heart disease” and “cerebrovascular disease (cerebral stroke)” have been cited as three major causes of death in Japan. Cancer causes the highest number of fatalities among these three major causes, accounting for 30% of all fatalities.
When cancers are classified based on the sites of occurrence, they can be classified into lung cancer, stomach cancer, colon cancer, and liver cancer in descending order of the number of patients affected in Japan. However, the 5-year relative survival of patients with stomach cancer or colon cancer is around 60%, which is relatively high.
In contrast, the 5-year relative survival of patients with lung cancer or liver cancer is around 18%, which is relatively low. In this way, it is known that therapeutic prognoses of lung cancer and liver cancer are poor.
Liver tumor, which is a tumor occurring in the liver, is classified roughly into three types: primary hepatocarcinoma, metastatic hepatocarcinoma, and hemangioma. Primary hepatocarcinoma is a malignant tumor originating in the hepatic cells.
Metastatic hepatocarcinoma is a secondary malignant tumor occurring due to metastasis to a liver of cancer cells that developed in other organs. Primary hepatocarcinoma and metastatic hepatocarcinoma are believed to be liver tumors leading to liver cancer. On the other hand, hemangioma (hepatic hemangioma) is a benign tumor formed by numerous large and small blood vessels intertwining with each other.
However, because primary hepatocarcinoma and metastatic hepatocarcinoma occasionally that have forms similar to that of hepatic hemangioma sometimes occur, observation of the clinical course is required.
Moreover, the degree of malignancy of primary hepatocarcinoma differs depending on the degree of differentiation of neoplastic hepatic cells (degree of maturation of hepatic cells).
Specifically, the degree of malignancy is higher when there are fewer instances of division of hepatic cells during the period of tumorigenic transformation (i.e., when the degree of progression of differentiation from hepatic stem cells to hepatic cells is immature).
Therefore, if a liver tumor is found, it is important to distinguish whether the liver tumor found is any of a primary hepatocarcinoma, metastatic hepatocarcinoma, or hemangioma.
Moreover, if the liver tumor found is a primary hepatocarcinoma, it is necessary to promptly identify its degree of malignancy (degree of differentiation) in its level and formulate a treatment plan according to the characteristics of the liver tumor in order to improve the therapeutic prognosis of the liver cancer.
Therefore, studies are being conducted in which liver tumors are identified in ultrasound diagnoses using a contrast agent.
Specifically, it is to identify liver tumors with a contrast echo method that acquires ultrasonic images using microbubbles that can be intravenously administered as an ultrasonic contrast agent.
According to the contrast echo method, blood-flow signals are enhanced by microbubbles introduced into the blood vessels. This allows a physician to clearly observe the blood-flow dynamics by referring to ultrasonic images using the contrast agent. Furthermore, the microbubbles are characterized by being taken up by Kupffer cells in the liver via the blood vessels to specifically undergo phagocytosis.
In a liver tumor, because Kupffer cells have decreased to a greater extent than in the normal tissues, the degree of uptake of microbubbles is reduced. Consequently, in a liver tumor, echo reflections will have low signals due to the microbubbles. This makes it possible for the physician to clearly observe the form of the liver tumor by referring to ultrasonic images using the contrast agent.
Structures in the liver stained with the ultrasonic contrast agent are classified roughly into the blood vessels, the portal vein, and the hepatic parenchyma. The process from injecting the ultrasonic contrast agent into the subject to staining of the blood vessels, the portal vein, and the hepatic parenchyma is briefly described in sequence below.
First, because the contrast agent injected into the subject flows into the liver through the blood vessels, the blood vessels are stained (early vascular phase, or arterial phase: a time zone before approximately 40 seconds elapse after the contrast agent is injected).
Then, because the contrast agent flows into the portal vein, the portal vein is stained (late vascular phase, or portal vein phase: a time zone centered on approximately 90 seconds after the contrast agent is injected). Subsequently, the contrast agent is taken up by the hepatic cells and the hepatic parenchyma is stained. Moreover, because the contrast agent in the blood vessels or portal vein is swept away by the blood flow, the blood vessels and the portal vein are no longer stained (parenchymal phase: a time zone centered on approximately 5 minutes after the contrast agent is injected).
Recently, detailed analyses have been performed on staining patterns along the time series from the early vascular phase leading to the parenchymal phase via the late vascular phase in a liver tumor. As a result, it has been revealed that each liver tumor type (primary hepatocarcinoma, metastatic hepatocarcinoma, and hemangioma) has specific tendencies in its staining patterns along the time series (e.g., “Differential diagnosis of neoplastic lesion of the liver using Levovist.” Rad Fan Vol. 2 No. 2: 62-65, 2004). Furthermore, it has been revealed that primary hepatocarcinoma has specific tendencies in its staining patterns along the time series depending on the degree of differentiation (e.g. “Findings from contrast of hepatocellular carcinoma (HCC): Attempt to diagnose the degree of differentiation using Levovist.” Rad Fan Vol. 2 No. 2: 66-68, 2004).
The staining patterns by type of liver tumor will be described with reference to FIG. 1. FIG. 1 is a diagram for describing the staining patterns by type of liver tumor. In addition, FIG. 1 is a diagram showing ultrasonic images acquired along the time series and schematically shows the staining patterns in the periphery centered on the liver tumor.
As shown in FIG. 1, the staining patterns of primary hepatocarcinoma show that from the early vascular phase to the late vascular phase, the entire liver region is gradually stained. Moreover, the staining patterns of primary hepatocarcinoma show that in the parenchymal phase, portions of the liver tumor other than the internal region and the hepatic parenchyma around the liver tumor are stained.
Moreover, the staining patterns of metastatic hepatocarcinoma show that from the early vascular phase to the late vascular phase, the region from the outside leading to the inside centered on the boundary of the liver tumor is gradually stained. Moreover, the staining patterns of metastatic hepatocarcinoma show that in the parenchymal phase, the entire liver tumor is not stained and the hepatic parenchyma around the liver tumor is stained.
Moreover, the staining patterns of hemangioma show that from the early vascular phase to the late vascular phase, the regions other than the internal region of the liver tumor are gradually stained.
Moreover, the staining patterns of hemangioma show that in the parenchymal phase, portions of the liver tumor other than the internal region and the hepatic parenchyma around the liver tumor are stained.
Next, with reference to FIG. 2, the staining patterns for each degree of differentiation of primary hepatocarcinoma will be described.
FIG. 2 is a diagram showing the staining patterns for each degree of differentiation of primary hepatocarcinoma. In addition, FIG. 2 is a diagram schematically showing the staining patterns within the liver tumor region where the liver tumor is a primary hepatocarcinoma.
In the liver tumor identified as a primary hepatocarcinoma, if the degree of differentiation of neoplastic hepatic cells is high and there are dysplastic nodules that are either malignant or benign, the staining pattern tends to be “no staining in the early vascular phase, weak staining in the late vascular phase, and weak staining in the parenchymal phase” as in the pattern A shown in FIG. 2.
Moreover, in the liver tumor identified as a primary hepatocarcinoma, if well-differentiated hepatic cells have become a malignant tumor, the staining pattern tends to be “weak staining” throughout the early vascular phase, late vascular phase, and parenchymal phase as in the pattern B.
Moreover, as the degree of differentiation of neoplastic hepatic cells becomes lower (as the degree of malignancy becomes higher) from the status shown in the pattern B, the staining pattern becomes those patterns shown in the pattern C, pattern D, and pattern E. Namely, the pattern C tends to be “weak staining in the early vascular phase, staining equivalent to that of the surrounding hepatic parenchyma in the late vascular phase, and staining equivalent to that of the surrounding hepatic parenchyma in the parenchymal phase”. The pattern D, which has a lower degree of differentiation than the pattern C, tends to be “weak staining in the early vascular phase, no staining in the late vascular phase, and no staining in the parenchymal phase”.
The moderately differentiated pattern E, which has a lower degree of differentiation than the pattern D, tends to be “intensive staining in the early vascular phase, weak staining in the late vascular phase, and no staining in the parenchymal phase”.
Namely, by interpreting images while comparing the staining patterns of liver tumors revealed by the recent study results as shown in FIGS. 1 and 2 with ultrasonic images representing the liver stained with the ultrasonic contrast agent, the physician can identify each liver tumor.
On the other hand, in the above-mentioned technology, there was a problem in that objective results for identifying the liver tumor could not be obtained quickly.
Namely, in the above-mentioned technology, the physician visually checks ultrasonic images in each time phase displayed in parallel to determine the staining pattern in each time phase. Then, after comprehending the combination of changes of the pattern represented in the staining patterns, the physician identifies the type of liver tumor. In this way, subjective elements are included in identification, thereby reducing the objectivity of the results of identification. Moreover, there was a problem in that the identification itself took time.
Moreover, as shown in FIG. 2, if the liver tumor is a primary hepatocarcinoma, the referred staining pattern shows various tendencies. Therefore, there is also an absence of objectivity in the results of identification in cases of visually identifying the degree of malignancy of a primary hepatocarcinoma. Moreover, there was a problem in that the identification itself took time.
Therefore, the applicant filed a patent application of an image processing apparatus, an ultrasonic imaging apparatus, and an image processing program that can quickly obtain objective results for identifying a liver tumor (patent application No. 2008-170408). The invention according to this patent application acquires a plurality of ultrasonic images by ultrasonically capturing a subject along a time series to which a contrast agent has been administered. Then, staining patterns of the contrast agent along the time series are classified by the type of liver tumor. Then, based on the staining patterns by type, the type of liver tumor set in the plurality of ultrasonic images is determined. In this way, the staining patterns of the contrast agent are quantitatively analyzed to determine the type of liver tumor.
On the other hand, it has been reported that liver tumors can be distinguished by analyzing the hemodynamics within the liver tumor region (“Correlation Between the Blood Supply and Grade of Malignancy of Hepatocellular Nodules Associated with Liver Cirrhosis: Evaluation by CT During Intraarterial Injection of Contrast Medium.” AJR: 172, April 1999 P. 969-976).
Namely, this is a method of judging the degree of malignancy based on the blood flow volume within the liver tumor and the information of which is dominant, either the arterial blood flow volume or the blood flow volume in the portal vein. With reference to FIG. 3, the correlation between the degree of malignancy (degree of differentiation) of a liver tumor and the blood flow volume will be described. FIG. 3 is a diagram showing the correlation between the degree of malignancy of a liver tumor and the blood flow volume.
FIG. 3 shows the correlation between the arterial blood flow volume that nourishes healthy hepatic cells, the arterial blood flow volume that nourishes the tumor, and the blood flow volume in the portal vein, with the degree of malignancy of the liver tumor. For example, if the blood flow volume in the portal vein is higher than the arterial blood flow volume (i.e., the blood flow volume in the portal vein is more dominant than the arterial blood flow volume), the degree of malignancy of the liver tumor is classified as class 1, which indicates a low degree of malignancy. On the other hand, as the arterial blood flow volume that nourishes the tumor increases and the arterial blood flow volume and the blood flow volume in the portal vein that nourishes healthy hepatic cells decreases, the degree of malignancy gradually becomes higher. When the blood flow volume is only the arterial blood flow volume that nourishes the tumor, the degree of malignancy of the liver tumor is classified as class 6, which indicates the highest degree of malignancy.
As described above, based on the dominance relationship between the arterial blood flow volume and the blood flow volume in the portal vein, it is possible to judge the degree of malignancy of liver tumor. However, in the above-mentioned patent application (patent application No. 2008-170408), there are no descriptions of any method of determining the degree of malignancy of liver tumor based on the dominance relationship between the arterial blood flow volume and the blood flow volume in the portal vein.
Moreover, in the above-mentioned patent application (patent application No. 2008-170408), there are no descriptions of any method of obtaining the boundary time between the early vascular phase (arterial phase) and the late vascular phase (portal vein phase). Herein, the arterial phase is a time phase in which only the arteries are intensively stained after the contrast agent is injected. Moreover, the portal vein phase is a time phase in which the portal vein is stained after the arterial phase. However, in the portal vein phase, the contrast agent has not completely escaped from the arteries. Therefore, in the portal vein phase, both the arteries and the portal vein are stained.
There is no established method of quantitatively obtaining the boundary time phase between the arterial phase and the portal vein phase. Therefore, the physician visually checks ultrasonic images to subjectively judge the boundary time phase. In this way, the boundary time phase between the arterial phase and the portal vein phase is not objectively obtained, and it is therefore likely that the accuracy of generating staining patterns in the arterial phase or the accuracy of determining the type of liver tumor are affected.